Bioinspired microcapsule reactor with engineered probiotics for IBD therapy.

Although probiotic-based bionic strategies show therapeutic promise for inflammatory bowel disease, their clinical translation is limited by poor gastric acid survival, inefficient intestinal colonization and inadequate targeting. Inspired by the multi-level cooperative mechanism of defense protection-danger sensing-tissue repair observed in coral communities, we developed a core-shell bionic microcapsule reactor (MY-E@SS). Here we show that the multifunctional bionic shell enables safe delivery of engineered bacteria through the gastrointestinal tract. Upon reaching inflamed intestinal sites, these bacteria sense the pathological microenvironment and responsively release an anti-inflammatory peptide. In a male murine model of inflammatory bowel disease, this system exhibited excellent biocompatibility and pronounced therapeutic efficacy, restoring intestinal barrier integrity, attenuating systemic inflammation and oxidative stress, modulating respiratory metabolism, and reestablishing microbial homeostasis. Mechanistically, therapeutic effects were attributed to inhibition of TNF-α/NF-κB signaling pathway. This work provides an intelligent platform to modulate inflammatory microenvironments and advance therapies for complex diseases.